The most common burden of epilepsy, reported by epilepsy patients themselves, is the lack of predictability of their seizures. While seizures occur infrequently and are unpredictable, interictal epileptiform discharges (IEDs) are isolated epileptiform discharges between seizures that can occur relatively frequently; up to several times per second. While IEDs are associated with epilepsy, little is known about the underlying physiology of IEDs and the relationship between IEDs and seizures remains a mystery. The overall goal of our research proposal is to understand the spatial propagation of IEDs and their relationship to the seizure core with the potential for evaluating spatial and neuronal properties of IEDs as predictive tools for localizing when and where a seizure happens. The significant barriers to studying the relationship between IEDs and seizures in humans stem from the low resolution of clinical recordings, which also makes these recordings difficult to compare to more mechanistic studies of IEDs in animals. We will address this gap by examining thousands of IEDs recorded from microelectrode arrays in 11 human epilepsy patients. These arrays subsample approximately the same area recorded by a standard clinical electrode with 96 penetrating microelectrodes. The density of these arrays and their ability to record single unit activity will allow us to translate between clinical intracranial EEG and single human neuron activity. We propose to understand IED neurophysiology relative to the seizure onset zone via the following three Specific Aims. Aim 1 will elucidate how IEDs travel across the cortex, relative to the location of the seizure onset zone. We hypothesize that IEDs will propagate towards the seizure onset zone and will become more consistent as a seizure approaches. Aim 2 will focus on understanding neuronal firing and high frequency LFP correlates of IEDs in order to determine a correlate of distance from the seizure onset zone. Together, these aims will improve our understanding of the neurophysiology of IEDs and how physiological features of IEDs relate to the seizure onset zone. Any reduction in uncertainty that can be gleaned about seizure occurrence from IEDs will be highly valuable for epilepsy patients? everyday lives. These experiments will therefore be important for understanding the neuronal and spatial properties of IEDs, which will aid in the diagnosis and treatment of medically refractory epilepsy.